Membrane Insertion of C-tail Anchored Proteins

The correct localization of proteins is essential for cell viability. In order to achieve correct protein localization to cellular membranes, conserved membrane targeting and translocation mechanisms have evolved. The focus of this work was membrane targeting and translocation of a group of proteins that circumvent the known targeting and translocation mechanisms, the C-tail anchored protein family. Members of this protein family carry out a wide range of functions, from protein translocation and recognition events preceding membrane fusion, to the regulation of programmed cell death. In this work, the mechanisms of membrane insertion and targeting of two C-tail anchored proteins were studied utilizing in vivo and in vitro methods, in yeast and mammalian cell systems. The proteins studied were cytochrome b(5), a well characterized C-tail anchored model protein, and N-Bak, a novel member of the Bcl-2 family of regulators of programmed cell death. Membrane insertion of cytochrome b(5) into the endoplasmic reticulum membrane was found to occur independently of the known protein conducting channels, through which signal peptide-containing polypeptides are translocated. In fact, the membrane insertion process was independent of any protein components and did not require energy. Instead membrane insertion was observed to be dependent on the lipid composition of the membrane. The targeting of N-Bak was found to depend on the cellular context. Either the mitochondrial or endoplasmic reticulum membranes were targeted, which resulted in morphological changes of the target membranes. These findings indicate the existence of a novel membrane insertion mechanism for C-tail anchored proteins, in which membrane integration of the transmembrane domain, and the translocation of C-terminal fragments, appears to be spontaneous. This mode of membrane insertion is regulated by the target membrane fluidity, which depends on the lipid composition of the bilayer, and the hydrophobicity of the transmembrane domain of the C-tail anchored protein, as well as by the availability of the C-tail for membrane integration. Together these mechanisms enable the cell to achieve spatial and temporal regulation of sub-cellular localization of C-tail anchored proteins.

Network Knowledge versus Cluster Knowledge- The Gordian Knot of Knowledge Transfer Concepts

Both management scholars and economic geographers have studied knowledge and argued that the ability to transfer knowledge is critical to competitive success. Networks and other forms for cooperation are often the context when analyzing knowledge transfer within management research, while economic geographers focus on the role of the cluster for knowledge transfer and creation. With the common interest in knowledge transfer, few attempts to interdisciplinary research have been made. The aim of this paper is to outline the knowledge transfer concepts in the two strands of literature of management and economic geography (EG). The paper takes an analytical approach to review the existing contributions and seek to identify the benefits of further interaction between the disciplines. Furthermore, it offers an interpretation of the concepts of cluster and network, and suggests a clearer distinction between their respective definitions. The paper posits that studies of internal networks transcending national borders and clusters are not necessarily mutually exclusive when it comes to transfer of knowledge and the learning process of the firm. Our conclusion is that researchers in general seem to increasingly acknowledge the importance of studying both the effect of and the need for geographical proximity and external networks for the knowledge transfer process, but that there exists equivocalness in defining clusters and networks.